A 27-year-old male presents to his primary care physician complaining of pain with urination and eye redness. He reports that he developed these symptoms approximately one week ago. He also has noticed left knee and right heel pain that started a few days ago. He denies any recent trauma. He had an episode of abdominal pain and diarrhea ten days ago that resolved. He has otherwise felt well. On exam, he walks with a limp and his conjunctivae are erythematous. Laboratory findings are notable for an elevated erythrocyte sedimentation rate (ESR) and elevated C-reactive protein (CRP). Which of the following is most likely associated with this patient’s condition?

Anti-cyclic citrullinated peptide (anti-CCP) antibody

A medical examiner was called to investigate the death of a 75-year-old type 1 diabetic Caucasian male who was a retired physician. His caretaker discovered his body in the bedroom with an empty syringe and a small bottle of lispro lying on the nightstand. She explains that his wife of 50 years passed away six months ago and that he had no children or family. He had become extremely depressed and did not want to live anymore. Which of the following would be most consistent with his blood chemistry if a blood sample were taken?

Glucose: 25 mg/dL, high insulin and absent C-peptide levels

Glucose: 95 mg/dL, high insulin and C-peptide levels

Glucose: 95 mg/dL, low insulin and low C-peptide levels

Glucose: 25 mg/dL, high insulin and high C-peptide levels

Glucose: 25 mg/dL, high insulin and normal C-peptide levels

A father brings his 3-year-old son to the pediatrician because he is concerned about his health. He states that throughout his son's life he has had recurrent infections despite proper treatment and hygiene. Upon reviewing the patient's chart, the pediatrician notices that the child has been infected multiple times with S. aureus, Aspergillus, and E. coli. Which of the following would confirm the most likely cause of this patient's symptoms?

Negative nitroblue-tetrazolium test

Increased IgM, Decreased IgG, IgA, and IgE

Positive nitroblue-tetrazolium test

Normal dihydrorhodamine (DHR) flow cytometry test

Increased IgE and IgA, Decreased IgM

A 20-year-old woman presents with shortness of breath and chest pain for 1 week. She says the chest pain is severe, sharp in character, and aggravated upon deep breathing. She says she becomes short of breath while walking upstairs in her home or with any type of exertion. She says she frequently feels feverish and fatigued. No significant past medical history and no current medications. Review of systems is significant for a weight loss of 4.5 kg (10.0 lb) over the past month and joint pain in her wrists, hands, and knees. Vital signs are within normal limits. On physical examination, there is a pink rash over her face which is aggravated by sunlight (shown in the image). There are decreased breath sounds on the right. A chest radiograph reveals evidence of a right-sided pleural effusion. Routine urinalysis and urine dipstick are normal. Serum antinuclear antibody (ANA) and anti-double-stranded DNA levels are positive. The patient is started on prednisone therapy and 2 weeks later her CBC is obtained and compared to the one on admission: On admission Leukocytes 8,000/mm3 Neutrophils 60% Lymphocytes 23% Eosinophils 2% Basophils 1% Monocyte 5% Hemoglobin 10 g/dL Creatinine 0.8 mg/dL BUN 15 mg/dL 2 weeks later Leukocytes 13,000/mm3 Neutrophils 90% Lymphocytes 8% Eosinophils 0% Basophils 0% Monocyte 1% Hemoglobin 12g/dL Creatinine 0.8 mg/dL BUN 15 mg/dL Which of the following best describes the most likely mechanism that accounts for the difference between these 2 complete blood counts (CBCs)?

Downregulation of neutrophil adhesion molecules

Redistribution of neutrophils in the lymph nodes

Upregulation of cellular adhesion molecules in the endothelium

A 29-year-old woman comes to the clinic for complaints of fatigue and palpitations for the past 3 days. She reports that even standing up and walking around takes “a lot of energy.” She was forced to call in sick today to her work as a kindergarten teacher. She denies any previous episodes but does endorse symmetric joint pain of her hands, wrists, knees, and ankles that was worse in the morning over the past week that self-resolved. She also reports a runny nose and congestion. Past medical history is unremarkable. Physical examination demonstrates splenomegaly, pallor, and generalized weakness; there is no lymphadenopathy. What is the most likely explanation for this patient’s symptoms?

Infection with Epstein-Barr virus

Substitution of glutamic acid with valine at the beta chain

A 36-year-old woman presents with thyroid swelling. She has been healthy until now and follows all the healthcare precautions except for missing a flu shot this year. On physical examination, the thyroid gland is diffusely enlarged and tender to palpation. Laboratory findings show a decreased serum TSH level and elevated erythrocyte sedimentation rate. Which of the following histopathologic findings would most likely be found in the thyroid gland of this patient?

Mixed cellular infiltration with multinuclear giant cells

Extensive fibrosis of the stroma

Lymphocytic infiltration with germinal centers

Orphan Annie nuclei with psammoma bodies

Sheets of polygonal cells in amyloid stroma

Inflammatory markers in laboratory testing for USMLE Step 1: High-Yield Pathology Lessons

Inflammatory Markers - The Body's Alarm Bells

Erythrocyte Sedimentation Rate (ESR)
- Indirect measure of acute phase response; ↑ fibrinogen coats RBCs, causing them to aggregate and sediment faster.
- Slow to rise and fall. Non-specific.
- Used to monitor conditions like temporal arteritis, polymyalgia rheumatica.
C-Reactive Protein (CRP)
- Acute-phase reactant from liver (induced by IL-6).
- Rises (4-6 hrs) and falls faster than ESR, better reflecting acute inflammation.
- More specific for bacterial infection & tissue necrosis.
Procalcitonin (PCT)
- Rises in response to bacterial toxins; suppressed by interferons in viral infections.
- Useful to distinguish bacterial from viral etiologies and guide antibiotic stewardship in sepsis.

⭐ In suspected Giant Cell (Temporal) Arteritis, an ESR > 50 mm/hr is a classic finding. A normal ESR has a high negative predictive value.

Key Protein Markers - The Pro Players

C-Reactive Protein (CRP)
- Opsonin; fixes complement & facilitates phagocytosis. Synthesized by the liver.
- Rises rapidly (within 4-6 hours) and falls quickly. More sensitive and specific than ESR for acute inflammation.
Erythrocyte Sedimentation Rate (ESR)
- Indirect measure of inflammation; reflects ↑ acute-phase reactants (especially fibrinogen), causing RBCs to form rouleaux and sediment faster.
- Slow to rise and fall. Influenced by RBC morphology, anemia, and age.
- 📌 Mnemonic: ESR is Elevated by Everything and is Slow-R.
Procalcitonin
- Specific for bacterial infections; levels rise significantly in response to bacterial toxins but not typically in viral or non-infectious inflammation.
- Useful for guiding antibiotic stewardship.

⭐ A markedly elevated ESR (>100 mm/hr) is classically associated with giant cell arteritis, polymyalgia rheumatica, and multiple myeloma.

PCT levels in sepsis vs. non-sepsis and survival

Negative Reactants - Taking a Nosedive

Proteins with ↓ serum concentration during inflammation due to hepatic reprioritization of synthesis.
Key markers include:
- Albumin: Long half-life (~20 days); ↓ suggests prolonged inflammation or malnutrition.
- Transferrin: Iron transport protein; ↓ contributes to anemia of chronic disease.
- Prealbumin (Transthyretin): Short half-life (~2 days); excellent for tracking acute nutritional changes.

⭐ Prealbumin's short half-life makes it a more sensitive indicator of real-time nutritional status and protein synthesis than albumin.

Clinical Interpretation - Connecting the Dots

Pattern Recognition: Interpreting markers together provides a clearer clinical picture than a single value.
Acute vs. Chronic: CRP is a real-time marker (rises/falls in 6-8 hrs), while ESR is a slow-reactor (changes over days-weeks).
Procalcitonin (PCT): More specific for bacterial infections vs. viral or autoimmune inflammation. A rise suggests bacterial sepsis.

Acute Phase Reactant Levels Over Time After Tissue Injury

⭐ In Systemic Lupus Erythematosus (SLE), ESR is often markedly elevated while CRP remains normal or only mildly elevated, a phenomenon known as 'CRP-ESR discordance'.

High‑Yield Points - ⚡ Biggest Takeaways

Erythrocyte Sedimentation Rate (ESR) is a non-specific marker influenced heavily by fibrinogen.

C-reactive protein (CRP), an acute-phase reactant from the liver, rises and falls more rapidly than ESR, making it useful for monitoring acute inflammation.

Procalcitonin is highly specific for bacterial infections and sepsis.

Ferritin is an acute-phase reactant; high levels can reflect inflammation, not just iron overload.

A "left shift" (↑ band neutrophils) with leukocytosis strongly suggests acute bacterial infection.

Continue reading on Oncourse

CONTINUE READING — FREE

or get the app

App Store|Google Play